Diisopropylethylamine → N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(2-(3-fluoroazetidin-1-yl)ethyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79449Notes

Reaction equation

HRID 79449 reaction equation
Cl.[F:2][CH:3]1[CH2:6][NH:5][CH2:4]1.CCN(C(C)C)C(C)C.[CH2:16]([C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][C:25]=2[NH:27][C:28]([C:30]2[N:34]3[CH:35]=[CH:36][C:37]([CH2:39][CH:40]=O)=[CH:38][C:33]3=[N:32][CH:31]=2)=[O:29])[N:20]([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([CH3:49])[N:44]=2)[N:19]=1)[CH3:17]>C(Cl)Cl.C(O)(=O)C>[CH2:16]([C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][C:25]=2[NH:27][C:28]([C:30]2[N:34]3[CH:35]=[CH:36][C:37]([CH2:39][CH2:40][N:5]4[CH2:6][CH:3]([F:2])[CH2:4]4)=[CH:38][C:33]3=[N:32][CH:31]=2)=[O:29])[N:20]([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([CH3:49])[N:44]=2)[N:19]=1)[CH3:17]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 101250543-fluoroazetidine HydrochlorideHCID 86672219N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(2-oxoethyl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 67260207N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(2-(3-fluoroazetidin-1-yl)ethyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 3-fluoroazetidine hydrochloride (61 mg, 0.55 mmol) in DCM (2 mL) was treated at ambient temperature with Hunig's base (0.10 mL, 0.57 mmol). To the hazy solution was added N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(2-oxoethyl)imidazo[1,2-a]pyridine-3-carboxamide (prepared according to (Example 127, Steps A-B; 50 mg, 0.11 mmol) (prepared according to the procedure for Example 127) and the (10 equivalents) was added, followed by 2 drops of glacial acetic acid, and the resulting mixture was stirred at ambient temperature for 16 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate solution, and extracted multiple times with DCM and EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate, concentrated under reduced pressure, and subjected to preparative thin-layer chromatography on silica, with a 10% MeOH-DCM mixture as eluent to afford the desired product (10 mg) as a white solid. MS (ES+APCI) m/z=512 (M+H) detected.

Workup

  1. customprepared
  2. customprepared
  3. additionwas added
  4. customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate solution
  5. extractionextracted multiple times with DCM and EtOAc
  6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ee324808184f47d98f8efca868d0ef89
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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